Evaluation of Treatment Efficacy According to Risk Group in Relapsed Childhood Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 10
- 主要终点
- Safety/Efficacy
研究概览
简要总结
This study is open-label, multi-center, prospective study, which targets childhood patients with relapsed acute lymphostatic leukemia including bone marrow recurrence. Aim of this study is to investigate the outcome of NGS MRD based risk stratified treatment for relapsed acute lymphoblastic leukemia in children and adolescents.
详细描述
The Risk Assessment is classified as follows based on the NGS-MRD results evaluated after EOI(End of Induction).
<Standard Risk>
- Late (Relapse ≥ 1 year after off treatment) B-ALL marrow or Combined relapse AND
- End of induction MRD < 0.01%
<High Risk>
- T-ALL marrow or combined relapse (any timing)
- All other B-ALL marrow or combined relapse cases
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 22 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients <= 1 year and >22 years of age at the time of relapse will be eligible
- •Participants must have a histologic diagnosis of acute lymphoblastic leukemia:
- •B-ALL: Precursor B-cell acute lymphoblastic leukemia
- •T-ALL: Precursor T-cell acute lymphoblastic leukemia
- •1st recurred acute lymphoblastic leukemia patients, recurred parts including marrow. Enrolling patients with combined extra medullary relapse including bone marrow is acceptable. (No limits for extra medullary site) Additionally, subjects whose blast cells in bone marrow are less than 5% (ALL whether type M2 or M3 must be definite)
- •Patients who have never received allogeneic stem cell transplant
- •Patients who have never received blinatumomab before
- •Adequate Renal Function
- •A serum creatinine based on age/gender as follows:
- •1 to < 2 years - Male (0.6) Female (0.6) 2 to < 6 years - Male (0.8) Female (0.8) 6 to < 10 years - Male (1) Female (1) 10 to < 13 years - Male (1.2) Female (1.2) 13 to < 16 years - Male (1.5) Female (1.4)
- •≥ 16 years - Male (1.7) Female (1.4)
- •Adequate Liver Function defined as a direct bilirubin <3.0 mg/dL
- •Adequate Cardiac Function defined as: Shortening fraction of ≥ 27% by echocardiogram, or Ejection fraction of ≥ 50% by echocardiogram
- •Lansky (age < 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60% at screening
- •Patients with a life expectancy of 1 or more year
- •Patients who are expected to comply with all required study procedures and follow the study protocol in the opinion of the investigator
- •Signed written informed consent and assent forms must be obtained prior to any study procedures
排除标准
- •Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia
- •Patients with Philadelphia chromosome positive (Ph+) ALL
- •Patients with CD19-negative recurrent progenitor B-cell acute lymphoblastic leukemia (non-expression of CD19 in peripheral blood or bone marrow by flow cytometry) are not eligible for administration of Blinatumomab
- •In case of relapsed within 1 month after the end of induction with the same 4-drug therapy used in this study
- •Patients with mixed phenotype leukemia
- •patient who was relapsed within 1 month after the end of induction therapy with the same 4-drug regimen to be used in this study.
- •Patients with genetic syndrome: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome bone marrow failure syndrome
- •Patients with known HIV
- •Female patients who are not proved as infertile or pregnant (Evidence of infertility: History taking of possibilities of pregnancy or urine human chorionic gonadotrophin test negative, amenorrhea more than a year, Natural or artificial (Ex.hormone therapy) menopause status more than a year, surgical sterilization(Ex.Hysterectomy or ovariotomy etc)
- •Currently receiving treatment in another investigational drug study or clinical trial
- •Evidence of unstable conditions that would pose a risk to subject safety or interfere with the patients' compliance
- •Patients with clinically relevant central nervous system (CNS) pathology or active CNS involvement including: unstable epilepsy, uncontrolled seizure, paralysis, aphasia, history of severe brain injury, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder
- •Known hypersensitivity to drugs or components to be administered: Idarubicin, Etoposide, Ifosfamide, Cytarabine, Vincristine, Mercaptopurine, Blinatumomab
研究组 & 干预措施
High Risk group with B-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> Blinatumomab 1st -> Blinatumomab 2nd -> HSCT
干预措施: Blinatumomab 1st(High Risk Group)_4 Weeks (Drug)
Standard Risk group with B-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> Repeat the Intensification course in parentheses 3 times(Intensification 1st -> Intensification 2nd -> Intensification 3rd -> Intensification 4th) -> Maintenance
干预措施: Reinduction(4weeks) (Drug)
Standard Risk group with B-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> Repeat the Intensification course in parentheses 3 times(Intensification 1st -> Intensification 2nd -> Intensification 3rd -> Intensification 4th) -> Maintenance
干预措施: Cosolodation 1st(3weeks) (Drug)
Standard Risk group with B-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> Repeat the Intensification course in parentheses 3 times(Intensification 1st -> Intensification 2nd -> Intensification 3rd -> Intensification 4th) -> Maintenance
干预措施: Consolidation 2nd(3weeks) (Drug)
Standard Risk group with B-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> Repeat the Intensification course in parentheses 3 times(Intensification 1st -> Intensification 2nd -> Intensification 3rd -> Intensification 4th) -> Maintenance
干预措施: Intensification course (Drug)
Standard Risk group with B-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> Repeat the Intensification course in parentheses 3 times(Intensification 1st -> Intensification 2nd -> Intensification 3rd -> Intensification 4th) -> Maintenance
干预措施: Maintenance(12 Weeks/Cycle) (Drug)
High Risk group with B-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> Blinatumomab 1st -> Blinatumomab 2nd -> HSCT
干预措施: Reinduction(4weeks) (Drug)
High Risk group with B-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> Blinatumomab 1st -> Blinatumomab 2nd -> HSCT
干预措施: Cosolodation 1st(3weeks) (Drug)
High Risk group with B-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> Blinatumomab 1st -> Blinatumomab 2nd -> HSCT
干预措施: Consolidation 2nd(3weeks) (Drug)
High Risk group with B-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> Blinatumomab 1st -> Blinatumomab 2nd -> HSCT
干预措施: Blinatumomab 2nd (High Risk Group)_4 Weeks (Drug)
High Risk group with B-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> Blinatumomab 1st -> Blinatumomab 2nd -> HSCT
干预措施: Stem Cell Transplantation (Procedure)
Very high Risk with B-ALL
Reinduction -> Blinatumomab-Salvage 1st -> Blinatumomab-Salvage 2nd -> HSCT
干预措施: Reinduction(4weeks) (Drug)
Very high Risk with B-ALL
Reinduction -> Blinatumomab-Salvage 1st -> Blinatumomab-Salvage 2nd -> HSCT
干预措施: Blinatumomab-Salvage 1st (Very High Risk Group)_4 Weeks (Drug)
Very high Risk with B-ALL
Reinduction -> Blinatumomab-Salvage 1st -> Blinatumomab-Salvage 2nd -> HSCT
干预措施: Blinatumomab-Salvage 2nd (Very High Risk Group)_4 Weeks (Drug)
Very high Risk with B-ALL
Reinduction -> Blinatumomab-Salvage 1st -> Blinatumomab-Salvage 2nd -> HSCT
干预措施: Intensification course (Drug)
T-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> HSCT
干预措施: Reinduction(4weeks) (Drug)
T-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> HSCT
干预措施: Cosolodation 1st(3weeks) (Drug)
T-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> HSCT
干预措施: Consolidation 2nd(3weeks) (Drug)
T-ALL
Reinduction -> Consolidation 1st -> Consolidation 2nd -> HSCT
干预措施: Stem Cell Transplantation (Procedure)
结局指标
主要结局
Safety/Efficacy
时间窗: through study completion, an average of 9 year
Patients with relapsed acute lymphoblastic leukemia are being treated after sorted into groups with their potential risk, and disease-free survival rate will be checked.
次要结局
- Death rate related to toxicity(through study completion, an average of 9 year)
- Disease-free survival rate (Blinatumomab)(through study completion, an average of 9 year)
- Disease-free survival rate (standard risk)(through study completion, an average of 9 year)
- Disease-free survival rate (Comparing minimal residual disease)(through study completion, an average of 9 year)
- Death rate related to treatment(through study completion, an average of 9 year)
- Toxicity rate during consolidation therapy(through study completion, an average of 9 year)
研究者
Ho Joon Im
Professor
Asan Medical Center